IQGA1_HUMAN
ID IQGA1_HUMAN Reviewed; 1657 AA.
AC P46940; A7MBM3;
DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1995, sequence version 1.
DT 03-AUG-2022, entry version 223.
DE RecName: Full=Ras GTPase-activating-like protein IQGAP1;
DE AltName: Full=p195;
GN Name=IQGAP1; Synonyms=KIAA0051;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Liver, and Placenta;
RX PubMed=8051149; DOI=10.1016/s0021-9258(17)32023-9;
RA Weissbach L., Settleman J., Kalady M.F., Snijders A.J., Murthy A.E.,
RA Yan Y.-X., Bernards A.;
RT "Identification of a human rasGAP-related protein containing calmodulin-
RT binding motifs.";
RL J. Biol. Chem. 269:20517-20521(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Bone marrow;
RX PubMed=7584044; DOI=10.1093/dnares/1.5.223;
RA Nomura N., Nagase T., Miyajima N., Sazuka T., Tanaka A., Sato S., Seki N.,
RA Kawarabayasi Y., Ishikawa K., Tabata S.;
RT "Prediction of the coding sequences of unidentified human genes. II. The
RT coding sequences of 40 new genes (KIAA0041-KIAA0080) deduced by analysis of
RT cDNA clones from human cell line KG-1.";
RL DNA Res. 1:223-229(1994).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP PROTEIN SEQUENCE OF 2-25; 81-88; 112-143; 192-230; 466-477; 557-585;
RP 923-935; 989-997; 1391-1397; 1466-1475 AND 1506-1516, CLEAVAGE OF INITIATOR
RP METHIONINE, ACETYLATION AT SER-2, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Colon carcinoma;
RA Bienvenut W.V., Lilla S., Zebisch A., Kolch W.;
RL Submitted (MAR-2009) to UniProtKB.
RN [6]
RP PROTEIN SEQUENCE OF 1441-1455, PHOSPHORYLATION AT SER-1443, INTERACTION
RP WITH CDC42 AND RAC1, DOMAIN, SUBCELLULAR LOCATION, AND IDENTIFICATION BY
RP MASS SPECTROMETRY.
RX PubMed=15355962; DOI=10.1074/jbc.m408113200;
RA Grohmanova K., Schlaepfer D., Hess D., Gutierrez P., Beck M.,
RA Kroschewski R.;
RT "Phosphorylation of IQGAP1 modulates its binding to Cdc42, revealing a new
RT type of rho-GTPase regulator.";
RL J. Biol. Chem. 279:48495-48504(2004).
RN [7]
RP PROTEIN SEQUENCE OF 1441-1455, PHOSPHORYLATION AT SER-1441 AND SER-1443,
RP MUTAGENESIS OF SER-1441 AND SER-1443, FUNCTION, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RX PubMed=15695813; DOI=10.1074/jbc.m413482200;
RA Li Z., McNulty D.E., Marler K.J.M., Lim L., Hall C., Annan R.S.,
RA Sacks D.B.;
RT "IQGAP1 promotes neurite outgrowth in a phosphorylation-dependent manner.";
RL J. Biol. Chem. 280:13871-13878(2005).
RN [8]
RP CHARACTERIZATION.
RX PubMed=8670801; DOI=10.1002/j.1460-2075.1996.tb00663.x;
RA Hart M.J., Callow M.G., Souza B., Polakis P.;
RT "IQGAP1, a calmodulin-binding protein with a rasGAP-related domain, is a
RT potential effector for cdc42Hs.";
RL EMBO J. 15:2997-3005(1996).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-2, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT networks.";
RL Cell 127:635-648(2006).
RN [10]
RP INTERACTION WITH TSG101.
RX PubMed=17853893; DOI=10.1038/sj.emboj.7601850;
RA Morita E., Sandrin V., Chung H.Y., Morham S.G., Gygi S.P., Rodesch C.K.,
RA Sundquist W.I.;
RT "Human ESCRT and ALIX proteins interact with proteins of the midbody and
RT function in cytokinesis.";
RL EMBO J. 26:4215-4227(2007).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1443, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [12]
RP INTERACTION WITH PAK6.
RX PubMed=18642328; DOI=10.1002/pros.20787;
RA Kaur R., Yuan X., Lu M.L., Balk S.P.;
RT "Increased PAK6 expression in prostate cancer and identification of PAK6
RT associated proteins.";
RL Prostate 68:1510-1516(2008).
RN [13]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, PHOSPHORYLATION [LARGE SCALE
RP ANALYSIS] AT SER-2; SER-330 AND SER-1443, CLEAVAGE OF INITIATOR METHIONINE
RP [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE
RP SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [14]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [15]
RP SUBCELLULAR LOCATION, AND FUNCTION.
RX PubMed=20883816; DOI=10.1016/j.biocel.2010.09.014;
RA Johnson M., Sharma M., Brocardo M.G., Henderson B.R.;
RT "IQGAP1 translocates to the nucleus in early S-phase and contributes to
RT cell cycle progression after DNA replication arrest.";
RL Int. J. Biochem. Cell Biol. 43:65-73(2011).
RN [16]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=22223895; DOI=10.1074/mcp.m111.015131;
RA Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T.,
RA Giglione C.;
RT "Comparative large-scale characterisation of plant vs. mammal proteins
RT reveals similar and idiosyncratic N-alpha acetylation features.";
RL Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012).
RN [17]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [18]
RP INTERACTION WITH SASH1.
RX PubMed=23333244; DOI=10.1016/j.cellsig.2012.12.025;
RA Zhou D., Wei Z., Deng S., Wang T., Zai M., Wang H., Guo L., Zhang J.,
RA Zhong H., He L., Xing Q.;
RT "SASH1 regulates melanocyte transepithelial migration through a novel
RT Galphas-SASH1-IQGAP1-E-cadherin dependent pathway.";
RL Cell. Signal. 25:1526-1538(2013).
RN [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-2; SER-330 AND SER-1443, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [20]
RP INTERACTION WITH EBOLAVIRUS VP40 (MICROBIAL INFECTION).
RX PubMed=23637409; DOI=10.1128/jvi.00470-13;
RA Lu J., Qu Y., Liu Y., Jambusaria R., Han Z., Ruthel G., Freedman B.D.,
RA Harty R.N.;
RT "Host IQGAP1 and Ebola virus VP40 interactions facilitate virus-like
RT particle egress.";
RL J. Virol. 87:7777-7780(2013).
RN [21]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [22]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [23]
RP INTERACTION WITH TMEM14B, SUBCELLULAR LOCATION, AND DEVELOPMENTAL STAGE.
RX PubMed=29033352; DOI=10.1016/j.stem.2017.08.013;
RA Liu J., Liu W., Yang L., Wu Q., Zhang H., Fang A., Li L., Xu X., Sun L.,
RA Zhang J., Tang F., Wang X.;
RT "The primate-specific gene TMEM14B marks outer radial glia cells and
RT promotes cortical expansion and folding.";
RL Cell Stem Cell 21:635-649(2017).
RN [24]
RP INTERACTION WITH HUMAN CYTOMEGALOVIRUS PROTEIN UL5 (MICROBIAL INFECTION).
RX PubMed=31739185; DOI=10.1016/j.virol.2019.10.018;
RA Anselmi G., Giuliani M., Vezzani G., Ferranti R., Gentile M., Cortese M.,
RA Amendola D., Pacchiani N., D'Aurizio R., Bruno L., Uematsu Y., Merola M.,
RA Maione D.;
RT "Characterization of pUL5, an HCMV protein interacting with the cellular
RT protein IQGAP1.";
RL Virology 540:57-65(2020).
RN [25]
RP STRUCTURE BY NMR OF 1559-1657.
RG RIKEN structural genomics initiative (RSGI);
RT "Solution structure of the carboxyl-terminal RGC domain in human IQGAP1.";
RL Submitted (SEP-2005) to the PDB data bank.
CC -!- FUNCTION: Plays a crucial role in regulating the dynamics and assembly
CC of the actin cytoskeleton. Binds to activated CDC42 but does not
CC stimulate its GTPase activity. It associates with calmodulin. Could
CC serve as an assembly scaffold for the organization of a multimolecular
CC complex that would interface incoming signals to the reorganization of
CC the actin cytoskeleton at the plasma membrane. May promote neurite
CC outgrowth (PubMed:15695813). May play a possible role in cell cycle
CC regulation by contributing to cell cycle progression after DNA
CC replication arrest (PubMed:20883816). {ECO:0000269|PubMed:15695813,
CC ECO:0000269|PubMed:20883816}.
CC -!- SUBUNIT: Interacts with CDC42; the interaction is demonstrated with
CC IQGAP1 in GTP-bound and in nucleotide-free state (PubMed:15355962).
CC Interacts with RAC1 (PubMed:15355962). Does not interact with RHOA.
CC Interacts with TSG101 (PubMed:17853893). Interacts with PAK6
CC (PubMed:18642328). Interacts with TMEM14B; this interaction increases
CC IQGAP1 phosphorylation and induces its nuclear translocation
CC (PubMed:29033352). Interacts with SASH1 (PubMed:23333244). Interacts
CC with PJVK (By similarity). {ECO:0000250|UniProtKB:Q9JKF1,
CC ECO:0000269|PubMed:15355962, ECO:0000269|PubMed:17853893,
CC ECO:0000269|PubMed:18642328, ECO:0000269|PubMed:23333244,
CC ECO:0000269|PubMed:29033352}.
CC -!- SUBUNIT: (Microbial infection) Interacts with ebolavirus vp40.
CC {ECO:0000269|PubMed:23637409}.
CC -!- SUBUNIT: (Microbial infection) Interacts with human cytomegalovirus
CC protein UL5. {ECO:0000269|PubMed:31739185}.
CC -!- INTERACTION:
CC P46940; O43707: ACTN4; NbExp=4; IntAct=EBI-297509, EBI-351526;
CC P46940; P56945: BCAR1; NbExp=4; IntAct=EBI-297509, EBI-702093;
CC P46940; P15056: BRAF; NbExp=4; IntAct=EBI-297509, EBI-365980;
CC P46940; Q9Y5K6: CD2AP; NbExp=4; IntAct=EBI-297509, EBI-298152;
CC P46940; P60953: CDC42; NbExp=11; IntAct=EBI-297509, EBI-81752;
CC P46940; P35222: CTNNB1; NbExp=3; IntAct=EBI-297509, EBI-491549;
CC P46940; P25025: CXCR2; NbExp=12; IntAct=EBI-297509, EBI-2835281;
CC P46940; P00533: EGFR; NbExp=4; IntAct=EBI-297509, EBI-297353;
CC P46940; P04626: ERBB2; NbExp=5; IntAct=EBI-297509, EBI-641062;
CC P46940; Q12905: ILF2; NbExp=3; IntAct=EBI-297509, EBI-357925;
CC P46940; P52954: LBX1; NbExp=3; IntAct=EBI-297509, EBI-20141748;
CC P46940; Q96QZ7: MAGI1; NbExp=4; IntAct=EBI-297509, EBI-924464;
CC P46940; A8MW99: MEI4; NbExp=3; IntAct=EBI-297509, EBI-19944212;
CC P46940; Q6FHY5: MEOX2; NbExp=3; IntAct=EBI-297509, EBI-16439278;
CC P46940; O60500: NPHS1; NbExp=5; IntAct=EBI-297509, EBI-996920;
CC P46940; Q9NP85: NPHS2; NbExp=4; IntAct=EBI-297509, EBI-6897706;
CC P46940; P32243-2: OTX2; NbExp=3; IntAct=EBI-297509, EBI-9087860;
CC P46940; O60331-4: PIP5K1C; NbExp=7; IntAct=EBI-297509, EBI-8838062;
CC P46940; Q96KN3: PKNOX2; NbExp=3; IntAct=EBI-297509, EBI-2692890;
CC P46940; O00592: PODXL; NbExp=4; IntAct=EBI-297509, EBI-6897823;
CC P46940; P63000: RAC1; NbExp=10; IntAct=EBI-297509, EBI-413628;
CC P46940; Q05823: RNASEL; NbExp=2; IntAct=EBI-297509, EBI-8390477;
CC P46940; Q96N21: TEPSIN; NbExp=3; IntAct=EBI-297509, EBI-11139477;
CC P46940; Q99816: TSG101; NbExp=5; IntAct=EBI-297509, EBI-346882;
CC P46940; O08808: Diaph1; Xeno; NbExp=8; IntAct=EBI-297509, EBI-1026445;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:15355962,
CC ECO:0000269|PubMed:29033352}. Nucleus {ECO:0000269|PubMed:20883816,
CC ECO:0000269|PubMed:29033352}. Cytoplasm {ECO:0000269|PubMed:20883816,
CC ECO:0000269|PubMed:29033352}. Note=Subcellular distribution is
CC regulated by the cell cycle, nuclear levels increase at G1/S phase
CC (PubMed:20883816). {ECO:0000269|PubMed:20883816}.
CC -!- TISSUE SPECIFICITY: Expressed in the placenta, lung, and kidney. A
CC lower level expression is seen in the heart, liver, skeletal muscle and
CC pancreas.
CC -!- DEVELOPMENTAL STAGE: Expressed widely in developing cortex.
CC {ECO:0000269|PubMed:29033352}.
CC -!- DOMAIN: Regions C1 and C2 can either interact with nucleotide-free
CC CDC42, or interact together, depending on the phosphorylation state of
CC Ser-1443. When Ser-1443 is not phosphorylated, C1 and C2 interact,
CC which prevents binding of nucleotide-free CDC42 and promotes binding of
CC GTP-bound CDC42. Phosphorylation of Ser-1443 prevents interaction
CC between C1 and C2, which opens the structure of the C-terminus and
CC allows binding and sequestration of nucleotide-free CDC42 on both C1
CC and C2. {ECO:0000269|PubMed:15355962}.
CC -!- PTM: Phosphorylation of Ser-1443 by PKC/PRKCE prevents interaction
CC between C1 and C2, allowing binding of nucleotide-free CDC42. Ser-1443
CC phosphorylation enhances the ability to promote neurite outgrowth.
CC {ECO:0000269|PubMed:15355962, ECO:0000269|PubMed:15695813}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA06123.2; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; L33075; AAA59187.1; -; mRNA.
DR EMBL; D29640; BAA06123.2; ALT_INIT; mRNA.
DR EMBL; CH471101; EAX02102.1; -; Genomic_DNA.
DR EMBL; BC151834; AAI51835.1; -; mRNA.
DR CCDS; CCDS10362.1; -.
DR PIR; A54854; A54854.
DR RefSeq; NP_003861.1; NM_003870.3.
DR PDB; 1X0H; NMR; -; A=1559-1657.
DR PDB; 2RR8; NMR; -; A=26-210.
DR PDB; 3FAY; X-ray; 2.20 A; A=962-1345.
DR PDB; 3I6X; X-ray; 2.50 A; A/B/C/D=1-191.
DR PDB; 5L0O; X-ray; 2.36 A; A/B/C/D=1-191.
DR PDBsum; 1X0H; -.
DR PDBsum; 2RR8; -.
DR PDBsum; 3FAY; -.
DR PDBsum; 3I6X; -.
DR PDBsum; 5L0O; -.
DR AlphaFoldDB; P46940; -.
DR BMRB; P46940; -.
DR SMR; P46940; -.
DR BioGRID; 114353; 457.
DR CORUM; P46940; -.
DR DIP; DIP-32597N; -.
DR IntAct; P46940; 240.
DR MINT; P46940; -.
DR STRING; 9606.ENSP00000268182; -.
DR ChEMBL; CHEMBL4295763; -.
DR DrugBank; DB11638; Artenimol.
DR CarbonylDB; P46940; -.
DR GlyGen; P46940; 2 sites, 2 O-linked glycans (2 sites).
DR iPTMnet; P46940; -.
DR MetOSite; P46940; -.
DR PhosphoSitePlus; P46940; -.
DR SwissPalm; P46940; -.
DR BioMuta; IQGAP1; -.
DR DMDM; 1170586; -.
DR EPD; P46940; -.
DR jPOST; P46940; -.
DR MassIVE; P46940; -.
DR MaxQB; P46940; -.
DR PaxDb; P46940; -.
DR PeptideAtlas; P46940; -.
DR PRIDE; P46940; -.
DR ProteomicsDB; 55776; -.
DR Antibodypedia; 2891; 422 antibodies from 41 providers.
DR DNASU; 8826; -.
DR Ensembl; ENST00000268182.10; ENSP00000268182.5; ENSG00000140575.13.
DR GeneID; 8826; -.
DR KEGG; hsa:8826; -.
DR MANE-Select; ENST00000268182.10; ENSP00000268182.5; NM_003870.4; NP_003861.1.
DR UCSC; uc002bpl.2; human.
DR CTD; 8826; -.
DR DisGeNET; 8826; -.
DR GeneCards; IQGAP1; -.
DR HGNC; HGNC:6110; IQGAP1.
DR HPA; ENSG00000140575; Low tissue specificity.
DR MIM; 603379; gene.
DR neXtProt; NX_P46940; -.
DR OpenTargets; ENSG00000140575; -.
DR PharmGKB; PA29910; -.
DR VEuPathDB; HostDB:ENSG00000140575; -.
DR eggNOG; KOG2128; Eukaryota.
DR GeneTree; ENSGT00950000183076; -.
DR HOGENOM; CLU_000972_2_1_1; -.
DR InParanoid; P46940; -.
DR OMA; HQKHFGG; -.
DR OrthoDB; 674320at2759; -.
DR PhylomeDB; P46940; -.
DR TreeFam; TF313078; -.
DR PathwayCommons; P46940; -.
DR Reactome; R-HSA-373753; Nephrin family interactions.
DR Reactome; R-HSA-381676; Glucagon-like Peptide-1 (GLP1) regulates insulin secretion.
DR Reactome; R-HSA-5626467; RHO GTPases activate IQGAPs.
DR Reactome; R-HSA-5674135; MAP2K and MAPK activation.
DR Reactome; R-HSA-6798695; Neutrophil degranulation.
DR Reactome; R-HSA-6802946; Signaling by moderate kinase activity BRAF mutants.
DR Reactome; R-HSA-6802948; Signaling by high-kinase activity BRAF mutants.
DR Reactome; R-HSA-6802952; Signaling by BRAF and RAF1 fusions.
DR Reactome; R-HSA-6802955; Paradoxical activation of RAF signaling by kinase inactive BRAF.
DR Reactome; R-HSA-8980692; RHOA GTPase cycle.
DR Reactome; R-HSA-9013106; RHOC GTPase cycle.
DR Reactome; R-HSA-9013148; CDC42 GTPase cycle.
DR Reactome; R-HSA-9013149; RAC1 GTPase cycle.
DR Reactome; R-HSA-9013404; RAC2 GTPase cycle.
DR Reactome; R-HSA-9013406; RHOQ GTPase cycle.
DR Reactome; R-HSA-9013420; RHOU GTPase cycle.
DR Reactome; R-HSA-9013424; RHOV GTPase cycle.
DR Reactome; R-HSA-9649948; Signaling downstream of RAS mutants.
DR Reactome; R-HSA-9656223; Signaling by RAF1 mutants.
DR SignaLink; P46940; -.
DR SIGNOR; P46940; -.
DR BioGRID-ORCS; 8826; 17 hits in 1086 CRISPR screens.
DR ChiTaRS; IQGAP1; human.
DR EvolutionaryTrace; P46940; -.
DR GeneWiki; IQGAP1; -.
DR GenomeRNAi; 8826; -.
DR Pharos; P46940; Tbio.
DR PRO; PR:P46940; -.
DR Proteomes; UP000005640; Chromosome 15.
DR RNAct; P46940; protein.
DR Bgee; ENSG00000140575; Expressed in calcaneal tendon and 208 other tissues.
DR ExpressionAtlas; P46940; baseline and differential.
DR Genevisible; P46940; HS.
DR GO; GO:0005884; C:actin filament; TAS:ProtInc.
DR GO; GO:0030424; C:axon; ISS:UniProtKB.
DR GO; GO:0030864; C:cortical actin cytoskeleton; IEA:Ensembl.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0036464; C:cytoplasmic ribonucleoprotein granule; IDA:ParkinsonsUK-UCL.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0031234; C:extrinsic component of cytoplasmic side of plasma membrane; IDA:UniProtKB.
DR GO; GO:0005925; C:focal adhesion; HDA:UniProtKB.
DR GO; GO:0030426; C:growth cone; ISS:UniProtKB.
DR GO; GO:0016328; C:lateral plasma membrane; IEA:Ensembl.
DR GO; GO:0005874; C:microtubule; IDA:UniProtKB.
DR GO; GO:0030496; C:midbody; IDA:UniProtKB.
DR GO; GO:0043005; C:neuron projection; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:1990904; C:ribonucleoprotein complex; IEA:Ensembl.
DR GO; GO:0001726; C:ruffle; IDA:UniProtKB.
DR GO; GO:0030667; C:secretory granule membrane; TAS:Reactome.
DR GO; GO:0036057; C:slit diaphragm; ISS:UniProtKB.
DR GO; GO:0051015; F:actin filament binding; IBA:GO_Central.
DR GO; GO:0045296; F:cadherin binding; HDA:BHF-UCL.
DR GO; GO:0005509; F:calcium ion binding; IDA:BHF-UCL.
DR GO; GO:0005516; F:calmodulin binding; IDA:BHF-UCL.
DR GO; GO:0005096; F:GTPase activator activity; IBA:GO_Central.
DR GO; GO:0005095; F:GTPase inhibitor activity; TAS:ProtInc.
DR GO; GO:0005078; F:MAP-kinase scaffold activity; IPI:BHF-UCL.
DR GO; GO:0060090; F:molecular adaptor activity; IDA:ARUK-UCL.
DR GO; GO:0005547; F:phosphatidylinositol-3,4,5-trisphosphate binding; IDA:UniProtKB.
DR GO; GO:0019904; F:protein domain specific binding; IPI:UniProtKB.
DR GO; GO:0019901; F:protein kinase binding; IPI:BHF-UCL.
DR GO; GO:0019903; F:protein phosphatase binding; IPI:UniProtKB.
DR GO; GO:0043539; F:protein serine/threonine kinase activator activity; IDA:BHF-UCL.
DR GO; GO:0044548; F:S100 protein binding; IPI:UniProtKB.
DR GO; GO:0031267; F:small GTPase binding; IPI:ARUK-UCL.
DR GO; GO:0016477; P:cell migration; IMP:ARUK-UCL.
DR GO; GO:0071277; P:cellular response to calcium ion; IDA:BHF-UCL.
DR GO; GO:0071364; P:cellular response to epidermal growth factor stimulus; IMP:BHF-UCL.
DR GO; GO:0036120; P:cellular response to platelet-derived growth factor stimulus; IEA:Ensembl.
DR GO; GO:0007173; P:epidermal growth factor receptor signaling pathway; IMP:BHF-UCL.
DR GO; GO:0008543; P:fibroblast growth factor receptor signaling pathway; IEA:Ensembl.
DR GO; GO:0010761; P:fibroblast migration; IEA:Ensembl.
DR GO; GO:0035305; P:negative regulation of dephosphorylation; IEA:Ensembl.
DR GO; GO:1990138; P:neuron projection extension; IMP:UniProtKB.
DR GO; GO:0048008; P:platelet-derived growth factor receptor signaling pathway; IEA:Ensembl.
DR GO; GO:0072015; P:podocyte development; ISS:UniProtKB.
DR GO; GO:0043410; P:positive regulation of MAPK cascade; IMP:BHF-UCL.
DR GO; GO:0045860; P:positive regulation of protein kinase activity; IMP:BHF-UCL.
DR GO; GO:0032956; P:regulation of actin cytoskeleton organization; IBA:GO_Central.
DR GO; GO:0001817; P:regulation of cytokine production; IEA:Ensembl.
DR GO; GO:0043087; P:regulation of GTPase activity; IEA:InterPro.
DR GO; GO:0007346; P:regulation of mitotic cell cycle; IMP:UniProtKB.
DR GO; GO:0007165; P:signal transduction; TAS:ProtInc.
DR CDD; cd00014; CH; 1.
DR CDD; cd00201; WW; 1.
DR Gene3D; 1.10.418.10; -; 1.
DR Gene3D; 1.10.506.10; -; 1.
DR InterPro; IPR001715; CH-domain.
DR InterPro; IPR036872; CH_dom_sf.
DR InterPro; IPR000048; IQ_motif_EF-hand-BS.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR000593; RasGAP_C.
DR InterPro; IPR023152; RasGAP_CS.
DR InterPro; IPR001936; RasGAP_dom.
DR InterPro; IPR008936; Rho_GTPase_activation_prot.
DR InterPro; IPR001202; WW_dom.
DR Pfam; PF00307; CH; 1.
DR Pfam; PF00612; IQ; 4.
DR Pfam; PF00616; RasGAP; 1.
DR Pfam; PF03836; RasGAP_C; 1.
DR SMART; SM00033; CH; 1.
DR SMART; SM00015; IQ; 4.
DR SMART; SM00323; RasGAP; 1.
DR SMART; SM00456; WW; 1.
DR SUPFAM; SSF47576; SSF47576; 1.
DR SUPFAM; SSF48350; SSF48350; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR PROSITE; PS50021; CH; 1.
DR PROSITE; PS50096; IQ; 4.
DR PROSITE; PS00509; RAS_GTPASE_ACTIV_1; 1.
DR PROSITE; PS50018; RAS_GTPASE_ACTIV_2; 1.
DR PROSITE; PS01159; WW_DOMAIN_1; 1.
DR PROSITE; PS50020; WW_DOMAIN_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Calmodulin-binding; Cell membrane; Cytoplasm;
KW Direct protein sequencing; Host-virus interaction; Membrane; Nucleus;
KW Phosphoprotein; Reference proteome; Repeat.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|Ref.5, ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:22223895, ECO:0007744|PubMed:22814378,
FT ECO:0007744|PubMed:25944712"
FT CHAIN 2..1657
FT /note="Ras GTPase-activating-like protein IQGAP1"
FT /id="PRO_0000056648"
FT DOMAIN 44..159
FT /note="Calponin-homology (CH)"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00044"
FT DOMAIN 679..712
FT /note="WW"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00224"
FT DOMAIN 745..774
FT /note="IQ 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00116"
FT DOMAIN 775..804
FT /note="IQ 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00116"
FT DOMAIN 805..834
FT /note="IQ 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00116"
FT DOMAIN 835..864
FT /note="IQ 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00116"
FT DOMAIN 1004..1237
FT /note="Ras-GAP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00167"
FT REGION 956..1274
FT /note="C1"
FT REGION 1276..1657
FT /note="C2"
FT REGION 1410..1448
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1413..1448
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 2
FT /note="N-acetylserine"
FT /evidence="ECO:0000269|Ref.5, ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:22223895, ECO:0007744|PubMed:22814378,
FT ECO:0007744|PubMed:25944712"
FT MOD_RES 2
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17081983,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163"
FT MOD_RES 172
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q9JKF1"
FT MOD_RES 330
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 1441
FT /note="Phosphoserine; by PKC"
FT /evidence="ECO:0000305|PubMed:15695813"
FT MOD_RES 1443
FT /note="Phosphoserine; by PKC/PRKCE"
FT /evidence="ECO:0000269|PubMed:15355962,
FT ECO:0000269|PubMed:15695813, ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163"
FT VARIANT 256
FT /note="S -> A (in dbSNP:rs12324924)"
FT /id="VAR_049134"
FT MUTAGEN 1441
FT /note="S->A: Abolishes neurite outgrowth promoting
FT activity; when associated with A-1443."
FT /evidence="ECO:0000269|PubMed:15695813"
FT MUTAGEN 1441
FT /note="S->E: Strongly enhances neurite outgrowth promoting
FT activity; when associated with A-1443."
FT /evidence="ECO:0000269|PubMed:15695813"
FT MUTAGEN 1443
FT /note="S->A: Abolishes neurite outgrowth promoting
FT activity; when associated with A-1441."
FT /evidence="ECO:0000269|PubMed:15695813"
FT MUTAGEN 1443
FT /note="S->D: Strongly enhances neurite outgrowth promoting
FT activity; when associated with A-1441."
FT /evidence="ECO:0000269|PubMed:15695813"
FT HELIX 31..58
FT /evidence="ECO:0007829|PDB:5L0O"
FT HELIX 65..67
FT /evidence="ECO:0007829|PDB:5L0O"
FT HELIX 70..72
FT /evidence="ECO:0007829|PDB:5L0O"
FT HELIX 76..85
FT /evidence="ECO:0007829|PDB:5L0O"
FT TURN 87..89
FT /evidence="ECO:0007829|PDB:5L0O"
FT HELIX 92..94
FT /evidence="ECO:0007829|PDB:5L0O"
FT TURN 96..99
FT /evidence="ECO:0007829|PDB:5L0O"
FT HELIX 101..105
FT /evidence="ECO:0007829|PDB:5L0O"
FT HELIX 110..112
FT /evidence="ECO:0007829|PDB:5L0O"
FT HELIX 113..125
FT /evidence="ECO:0007829|PDB:5L0O"
FT HELIX 130..132
FT /evidence="ECO:0007829|PDB:5L0O"
FT HELIX 136..140
FT /evidence="ECO:0007829|PDB:5L0O"
FT HELIX 145..161
FT /evidence="ECO:0007829|PDB:5L0O"
FT TURN 172..174
FT /evidence="ECO:0007829|PDB:5L0O"
FT HELIX 179..190
FT /evidence="ECO:0007829|PDB:5L0O"
FT HELIX 199..201
FT /evidence="ECO:0007829|PDB:2RR8"
FT TURN 206..208
FT /evidence="ECO:0007829|PDB:2RR8"
FT HELIX 962..981
FT /evidence="ECO:0007829|PDB:3FAY"
FT HELIX 984..991
FT /evidence="ECO:0007829|PDB:3FAY"
FT HELIX 1000..1009
FT /evidence="ECO:0007829|PDB:3FAY"
FT TURN 1010..1013
FT /evidence="ECO:0007829|PDB:3FAY"
FT HELIX 1016..1037
FT /evidence="ECO:0007829|PDB:3FAY"
FT STRAND 1039..1042
FT /evidence="ECO:0007829|PDB:3FAY"
FT HELIX 1043..1046
FT /evidence="ECO:0007829|PDB:3FAY"
FT HELIX 1050..1058
FT /evidence="ECO:0007829|PDB:3FAY"
FT HELIX 1062..1081
FT /evidence="ECO:0007829|PDB:3FAY"
FT HELIX 1091..1106
FT /evidence="ECO:0007829|PDB:3FAY"
FT HELIX 1118..1121
FT /evidence="ECO:0007829|PDB:3FAY"
FT HELIX 1125..1150
FT /evidence="ECO:0007829|PDB:3FAY"
FT HELIX 1151..1155
FT /evidence="ECO:0007829|PDB:3FAY"
FT HELIX 1158..1174
FT /evidence="ECO:0007829|PDB:3FAY"
FT HELIX 1180..1191
FT /evidence="ECO:0007829|PDB:3FAY"
FT HELIX 1192..1196
FT /evidence="ECO:0007829|PDB:3FAY"
FT HELIX 1197..1201
FT /evidence="ECO:0007829|PDB:3FAY"
FT TURN 1203..1207
FT /evidence="ECO:0007829|PDB:3FAY"
FT HELIX 1219..1236
FT /evidence="ECO:0007829|PDB:3FAY"
FT HELIX 1246..1248
FT /evidence="ECO:0007829|PDB:3FAY"
FT HELIX 1249..1270
FT /evidence="ECO:0007829|PDB:3FAY"
FT HELIX 1275..1278
FT /evidence="ECO:0007829|PDB:3FAY"
FT STRAND 1282..1284
FT /evidence="ECO:0007829|PDB:3FAY"
FT TURN 1285..1287
FT /evidence="ECO:0007829|PDB:3FAY"
FT STRAND 1290..1292
FT /evidence="ECO:0007829|PDB:3FAY"
FT HELIX 1299..1311
FT /evidence="ECO:0007829|PDB:3FAY"
FT HELIX 1313..1316
FT /evidence="ECO:0007829|PDB:3FAY"
FT HELIX 1323..1331
FT /evidence="ECO:0007829|PDB:3FAY"
FT STRAND 1561..1564
FT /evidence="ECO:0007829|PDB:1X0H"
FT HELIX 1565..1571
FT /evidence="ECO:0007829|PDB:1X0H"
FT STRAND 1572..1577
FT /evidence="ECO:0007829|PDB:1X0H"
FT HELIX 1583..1587
FT /evidence="ECO:0007829|PDB:1X0H"
FT STRAND 1589..1593
FT /evidence="ECO:0007829|PDB:1X0H"
FT STRAND 1596..1599
FT /evidence="ECO:0007829|PDB:1X0H"
FT STRAND 1601..1608
FT /evidence="ECO:0007829|PDB:1X0H"
FT STRAND 1615..1617
FT /evidence="ECO:0007829|PDB:1X0H"
FT HELIX 1619..1628
FT /evidence="ECO:0007829|PDB:1X0H"
FT STRAND 1632..1635
FT /evidence="ECO:0007829|PDB:1X0H"
FT TURN 1636..1638
FT /evidence="ECO:0007829|PDB:1X0H"
FT STRAND 1639..1642
FT /evidence="ECO:0007829|PDB:1X0H"
FT HELIX 1643..1652
FT /evidence="ECO:0007829|PDB:1X0H"
SQ SEQUENCE 1657 AA; 189252 MW; A52EC629596EAC33 CRC64;
MSAADEVDGL GVARPHYGSV LDNERLTAEE MDERRRQNVA YEYLCHLEEA KRWMEACLGE
DLPPTTELEE GLRNGVYLAK LGNFFSPKVV SLKKIYDREQ TRYKATGLHF RHTDNVIQWL
NAMDEIGLPK IFYPETTDIY DRKNMPRCIY CIHALSLYLF KLGLAPQIQD LYGKVDFTEE
EINNMKTELE KYGIQMPAFS KIGGILANEL SVDEAALHAA VIAINEAIDR RIPADTFAAL
KNPNAMLVNL EEPLASTYQD ILYQAKQDKM TNAKNRTENS ERERDVYEEL LTQAEIQGNI
NKVNTFSALA NIDLALEQGD ALALFRALQS PALGLRGLQQ QNSDWYLKQL LSDKQQKRQS
GQTDPLQKEE LQSGVDAANS AAQQYQRRLA AVALINAAIQ KGVAEKTVLE LMNPEAQLPQ
VYPFAADLYQ KELATLQRQS PEHNLTHPEL SVAVEMLSSV ALINRALESG DVNTVWKQLS
SSVTGLTNIE EENCQRYLDE LMKLKAQAHA ENNEFITWND IQACVDHVNL VVQEEHERIL
AIGLINEALD EGDAQKTLQA LQIPAAKLEG VLAEVAQHYQ DTLIRAKREK AQEIQDESAV
LWLDEIQGGI WQSNKDTQEA QKFALGIFAI NEAVESGDVG KTLSALRSPD VGLYGVIPEC
GETYHSDLAE AKKKKLAVGD NNSKWVKHWV KGGYYYYHNL ETQEGGWDEP PNFVQNSMQL
SREEIQSSIS GVTAAYNREQ LWLANEGLIT RLQARCRGYL VRQEFRSRMN FLKKQIPAIT
CIQSQWRGYK QKKAYQDRLA YLRSHKDEVV KIQSLARMHQ ARKRYRDRLQ YFRDHINDII
KIQAFIRANK ARDDYKTLIN AEDPPMVVVR KFVHLLDQSD QDFQEELDLM KMREEVITLI
RSNQQLENDL NLMDIKIGLL VKNKITLQDV VSHSKKLTKK NKEQLSDMMM INKQKGGLKA
LSKEKREKLE AYQHLFYLLQ TNPTYLAKLI FQMPQNKSTK FMDSVIFTLY NYASNQREEY
LLLRLFKTAL QEEIKSKVDQ IQEIVTGNPT VIKMVVSFNR GARGQNALRQ ILAPVVKEIM
DDKSLNIKTD PVDIYKSWVN QMESQTGEAS KLPYDVTPEQ ALAHEEVKTR LDSSIRNMRA
VTDKFLSAIV SSVDKIPYGM RFIAKVLKDS LHEKFPDAGE DELLKIIGNL LYYRYMNPAI
VAPDAFDIID LSAGGQLTTD QRRNLGSIAK MLQHAASNKM FLGDNAHLSI INEYLSQSYQ
KFRRFFQTAC DVPELQDKFN VDEYSDLVTL TKPVIYISIG EIINTHTLLL DHQDAIAPEH
NDPIHELLDD LGEVPTIESL IGESSGNLND PNKEALAKTE VSLTLTNKFD VPGDENAEMD
ARTILLNTKR LIVDVIRFQP GETLTEILET PATSEQEAEH QRAMQRRAIR DAKTPDKMKK
SKSVKEDSNL TLQEKKEKIQ TGLKKLTELG TVDPKNKYQE LINDIARDIR NQRRYRQRRK
AELVKLQQTY AALNSKATFY GEQVDYYKSY IKTCLDNLAS KGKVSKKPRE MKGKKSKKIS
LKYTAARLHE KGVLLEIEDL QVNQFKNVIF EISPTEEVGD FEVKAKFMGV QMETFMLHYQ
DLLQLQYEGV AVMKLFDRAK VNVNLLIFLL NKKFYGK
